Carthadex trial

Patients with Multiple Myeloma, ISS stage I -III age 18-65 yrs (must be transplant candidates) at first presentation; 145 patients.

Study design:
For patient numbers 111 to 145:

Induction treatment (before HDM/ASCT):
Carfilzomib 20mg/m2 for days 1,2, then 56mg/m2 days 8,9,15,16 of cycle 1, then 56mg/m2 throughout next cycles.
Thalidomide 200 mg days 1-28 of a 28 day cycle.
Dexamethasone 20 mg days 1,2,8,9,15,16 of a 28 day cycle.
8 cycles.

Consolidation treatment (guideline 8 weeks after HDM/ASCT):
Carfilzomib 56mg/m2 days 1,2,8,9,15,16 of a 28 day cycle.
Thalidomide 50 mg days 1-28 of a 28 day cycle.
Dexamethasone 20 mg days 1,2,8,9,15,16 of a 28 day cycle.
4 cycles.


Inclusion criteria

  • Patients with a confirmed diagnosis of multiple myeloma stage I to III according to the ISS criteria (see appendix I);
  • Age 18-65 years inclusive;
  • WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by co-morbid conditions) (see appendix II);
  • Negative urine pregnancy test at inclusion if applicable;
  • Written informed consent.

Exclusion Criteria

  • Known intolerance of Thalidomide;
  • Systemic AL amyloidosis;
  • Non-secretory MM;
  • Waldenstrom’s macroglobulinemia or IgM MM;
  • Previous chemotherapy or radiotherapy except 2 cycles of Melphalan/Prednisone
  • or local radiotherapy in case of local myeloma progression;
  • Severe cardiac dysfunction (NYHA classification II-IV, see appendix III);
  • Severe pulmonary dysfunction;
  • Significant hepatic dysfunction (serum bilirubin  30 mol/l or transaminases  3.0 times normal level), unless related to myeloma;
  • Creatinine clearance <15 cc/min;
  • Alkaline Phosphatase >3x ULN;
  • ANC < 1,0 x109/L, platelets < 75 x109/L, Hb < 4.9 mmol/L;
  • Intolerance to thromboprophylaxis;
  • Patients known to be HIV-positive;
  • Patients with active, uncontrolled infections;
  • Patients with neuropathy, CTC grade 3 or higher or grade 2 painful peripheral neuropathy;
  • Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
  • Patients (all males and all pre-menopausal women) who are not willing or capable to use adequate contraception during the therapy;
  • Lactating women;
  • WHO Performance status > 3.